The definition of labor is ‘the presence of uterine contractions of sufficient intensity, frequency, and duration to bring about demonstrable effacement and dilation of the cervix.’ See ACOG Practice Bulletin Number 49, December 2003: Dystocia and Augmentation of Labor. Obstetrics & Gynecology 2003; 102: 1445-54. From a clinical perspective, the characteristics of an efficient contraction are: (1) Pressure above 25 mm and regularity in intensity; (2) Frequency greater than 2 per 10 minutes and regularity in frequency; (3) Fundal dominance (contraction over the fundus and no appreciable contraction over the cervix); (4) Synchronization and fast propagation over the uterus. Currently progress of labor is determined by serial cervical exam to assess dilation, effacement and station.
In 2004 the cesarean delivery rate was 29.1% of all births, a new high for the U.S. (Martin J A et al. Preliminary births for 2004: Infant and maternal health. Health E-stats. National Center for Health Statistics. 11-15-0005) and well above the government's Healthy People 2000 goal of 15%. Unfortunately, the cesarean delivery rate continues to rise (6% in 2003-4), due both to an increase in the primary cesarean rate and a decrease in the rate of vaginal birth after cesarean (VBAC).
Labor Dystocia
The indications for cesarean delivery are varied, but dystocia (lack of progress in labor) leads the list. Dystocia is a labor abnormality resulting in abnormal progression and may be due to problems with power (uterine contractions and/or maternal expulsive effort), passenger (position or size of the fetus), or passage (shape or size of the birth canal). Early diagnosis and management of power problems are one of the concerns of this invention. If there are no contraindications (e.g., previa), protracted or arrested labors are often augmented with oxytocin. The goal of augmentation is to achieve minimally effective uterine activity; however, this is poorly defined and certainly inconsistent among parturients. Several groups have attempted to predict either antepartum, or early intrapartum, which patients are destined to have a labor dystocia. Unfortunately these efforts have met with little success. See Sheiner E et al. Risk factors and outcome of failure to progress during the first stage of labor: a population-based study. Acta Obstetricia et Gynecologica Scandinavica 2002; 81: 222-6; Feinstein U et al., Risk factors for arrest of descent during the second stage of labor. International Journal of Gynecology & Obstetrics 2002; 77: 7-14; Wilkes P T et al., Risk factors for cesarean delivery at presentation of nulliparous patients in Labor. Obstetrics and Gynecology 2003; 102: 1352-7; Turcot L et al., Multivariate analysis of risk factors for operative delivery in nulliparous women. American Journal of Obstetrics and Gynecology 1997; 176: 395-402; and Hin L Y et al., Antepartum and intrapartum prediction of cesarean need: Risk scoring in singleton pregnancies. Obstetrics and Gynecology 1997; 90: 183-6.
While most believe the cesarean delivery rate excessive, there is concern over efforts to reduce it. A litany of editorials followed an article in the New England Journal of Medicine arguing against aggressive reduction of cesareans (Sachs B P et al., The Risks of Lowering the Cesarean-Delivery Rate. The New England Journal of Medicine 1999; 340: 54-7). The subsequent Healthy People 2010 goals limit their focus on reducing the cesarean rate among only low risk patients (CDC and HRSA. Healthy People 2010: Maternal, Infant, and Child Health. http://www.healthypeople.gov/document/html/volume2/16mich.htm#_Toc494699664 (2006) 9-13-0006). The VBAC target is separately listed as 63%, quite distant from the rate of 10.6% reported in 2003 (Martin J A et al., Births: Final data for 2003. National vital statistics reports. National Center for Health Statistics 54(2). 9-8-2005. Hyattsville, Md. 9-13-0006). In fact the VBAC rate has actually fallen by nearly two-thirds since 1996, in large part due to safety concerns (Landon M B et al., the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network: Maternal and Perinatal Outcomes Associated with a Trial of Labor after Prior Cesarean Delivery. The New England Journal of Medicine 2004; 351: 2581-9). Women who labor and then fail to deliver vaginally have more complications (primarily infection and hemorrhage), incur more expense, and consume more resources (labor suite, nurse, etc.) than women who have an elective abdominal delivery. For VBAC patients, who are at increased risk for labor dystocia, the risk of uterine rupture increases the potential for a catastrophic outcome, and elective repeat cesareans are becoming the standard.
With declining numbers of patients attempting a subsequent vaginal birth after cesarean (VBAC), 60% of cesareans may relate directly or indirectly to the diagnosis of dystocia. The diagnosis of dystocia, however, is a matter of debate since, if given enough time, many very slow and even arrested labors will eventually proceed to vaginal delivery.
Preterm Labor
Preterm delivery is the most common cause of perinatal morbidity and mortality in infants without congenital anomalies. Over 11% of all births are preterm, and the complications of prematurity cause more than 70% of the deaths of nonanomalous fetuses and neonates (Gruver B. et al. Annual Summary of Vital Statistics—1996. Pediatrics 1997, 100(6):905-918).
Many studies have shown an association between having a short cervix on ultrasound and an increased risk of preterm delivery (Hasegawa I et al. Transvaginal ultrasonographic cervical assessment for the prediction of preterm delivery. Journal of Maternal and Fetal Medicine 1996, 5: 305-309; Murakawa H et al., Evaluation of threatened preterm delivery by transvaginal ultrasonographic measurement of cervical length. Obstetrics and Gynecology 1993, 82: 829-832; and Iams J D et al., Cervical competence as a continuum: a study of ultrasonographic cervical length and obstetrical performance. American Journal of Obstetrics and Gynecology, 1995, 172: 1097-1106). However neither this, nor any other test has proven sufficiently reliable for prediction.
Uterine Monitoring
The uterus is different from other visceral smooth muscles because it has no nerve plexus; it has no peristaltic waves, yet it displays tonus (contraction without shortening). Throughout most of pregnancy, the uterine contractions are minor and intensely localized. Only in the second half of gestation does the tendency for major contractions develop. These non-painful ‘Braxton Hicks’ contractions involve a large part or all of the myometrium, but usually lack the high degree of coordination that one finds during labor.
It is important to understand the impact of contractions on intrauterine pressure. Even when the uterus is relaxed its contents are under minimal pressure: the ‘diastolic uterine pressure.’ During contractions the intrauterine pressure increase depends on the elastic properties of the tissue and the active force exerted by the contractions of the myometrium. If the activity of the uterine musculature is coordinated and strong, the increase in pressure can be substantial (‘systolic uterine pressure’). However, if the coordination is weak, the same contraction strength gives rise to an overall increase of tonus reflected in an increase of systolic pressure. Intrauterine pressure, however, does not represent the direction or orientation of the forces acting on the fetus. It is known, for instance, that forces pushing down on the fetus (fundal uterine dominance) are more important to produce cervical dilation.
Cervical dilatation is the most important indicator of labor progress. The partogram—a graph of cervical dilation versus time—has been promoted by the World Health Organization for management of labor and recognition of abnormal progress (Rouse D J et al., Active-phase labor arrest: oxytocin augmentation for at least 4 hours. Obstetrics & Gynecology 1999; 93: 323-8). This graph has an ‘alert line’ at an active phase dilation rate of 1 cm/hour, used to guide transfer to a larger hospital and/or augmentation. More widely employed elsewhere in the world, use of the partogram may improve outcomes for both mother and fetus (Kwast B E et al., World-Health-Organization Partograph in Management of Labor. Lancet 1994; 343: 1399-404). The traditionally quoted 5th percentile of normal progress in spontaneous term labor is 1.2 cm/h for nulliparas and 1.5 cm/h for multiparas (Dujardin B et al., Value of the Alert and Action Lines on the Partogram. Lancet 1992; 339: 1336-8). However, these numbers have been challenged recently, with the 5th percentile for nulliparas recorded at <1 cm/hr, and periods of arrested dilation before 7 cm commonly seen (Friedman E A: Cervimetry—An Objective Method for the Study of Cervical Dilatation in Labor. American Journal of Obstetrics and Gynecology 1956; 71: 1189-93). Unfortunately, the inaccuracy of cervical dilation assessment severely limits the ability to detect a real change of one, or even two centimeters (Zhang J et al., Reassessing the labor curve in nulliparous women. American Journal of Obstetrics and Gynecology 2002; 187: 824-8). This may lead to incorrect conclusions regarding progress of labor in up to 33% of those progressing at 1 cm/hr, if checked at 2 hour intervals (Phelps J Y et al., Accuracy and intraobserver variability of simulated cervical dilatation measurements. American Journal of Obstetrics and Gynecology 1995; 173: 942-5).
Intrauterine pressure catheters (IUPCs) are currently used to measure the intra uterine pressure during rest (diastole) and during contraction (systole). However, it is impossible with an intra ovular method to distinguish different patterns of coordination over the uterus and also spatial characteristics of the contraction such as fundal dominance.
There are however, external methods to measure the local activity of the myometrium. Tocodynamometers can be applied externally over the mother's abdominal region and provide a local estimate of the changes in pressure, but not the internal pressure nor tonus. This is the most commonly employed uterine activity monitor.
Electrohysterography
It is well-established that uterine contractions are the result of uterine electrical activity (Wolfs G et al., An electromyographic study of the human uterus during labor. Obstet. Gynecol. 1971; 37: 241-6; and Wikland M, Lindblom B: Relationship between electrical and mechanical activity of the isolated term-pregnant human myometrium. Eur. J. Obstet. Gynecol. Reprod. Biol. 1985; 20: 337-46). This electrical activity can be observed non-invasively from the surface of the maternal abdomen and has been described in some detail (Buhimschi C et al., Electrical activity of the human uterus during pregnancy as recorded from the abdominal surface. Obstet. Gynecol. 1997; 90: 102-11; Jezewski J et al., Quantitative analysis of contraction patterns in electrical activity signal of pregnant uterus as an alternative to mechanical approach. Physiol Meas. 2005; 26: 753-67; Devedeux D et al., Uterine electromyography: a critical review. Am. J. Obstet. Gynecol. 1993; 169: 1636-53; and Mansour S et al., Uterine EMG spectral analysis and relationship to mechanical activity in pregnant monkeys. Med. Biol. Eng Comput. 1996; 34: 115-21). As early as 1950, this electrohysterogram (EHG) was found to discriminate between normal labor and ‘uterine inertia.’ See Steer C M, Hertsch G J: Electrical activity of the human uterus in labor; the electrohysterograph. Am. J Obstet Gynecol 1950; 59: 25-40; and Steer C M: The electrical activity of the human uterus in normal and abnormal labor. Am. J Obstet Gynecol 1954; 68: 867-90. Recently there has been renewed interest in the potential of EHG.
Several studies have investigated the utility of EHG in predicting preterm delivery. Verdenik et al. (Uterine electrical activity as predictor of preterm birth in women with preterm contractions. Eur. J. Obstet. Gynecol. Reprod. Biol. 2001; 95: 149-53) studied 47 women who presented with complaint of preterm contractions who were admitted either for tocodynamometer (toco) confirmation of contractions or for closer monitoring due to additional risk factors. Using two paramedian electrodes referenced to a ground, the filtered EMG was acquired for 30 minutes. The intensity of electrical activity was calculated as the root mean square (RMS) value of the entire signal. They also determined the median frequency of the power spectra, but only the RMS value differed in those patients who would deliver preterm (n=17) and those who reached term (n=30).
Agarwal et al. (Role of uterine artery velocimetry using color-flow Doppler and electromyography of uterus in prediction of preterm labor. J. Obstet. Gynaecol. Res. 2004; 30: 402-8) studied 100 patients at 24-32 weeks gestation at high risk for preterm labor and compared ultrasound cervical length measurement, uterine artery velocimetry and EHG in the prediction of labor outcome. EHG interpretation consisted of fast Fourier transform (FFT) analysis. Of the 89 subjects who completed the study, 27% delivered preterm. While Doppler indices correlated well with outcome, the DIG interpretation method employed was less successful. Only the mean amplitude at 0.1-Hz differed between the groups, and then only at recordings between 31 and 34 weeks gestation.
Maner et al. (Predicting term and preterm delivery with transabdominal uterine electromyography. Obstet. Gynecol. 2003; 101: 1254-60) investigated 99 women (57 term and 42 preterm) presenting with complaint of contractions. They were monitored with two sets of bipolar electrodes for 30-minutes. FFT was performed on the electrical bursts identified in the signals and the power spectrum peak frequency compared using ROC analysis. They were able to predict, with positive predictive value (PPV) of 0.85, which term patients would deliver within 24 hours. For preterm patients, they predicted delivery within four days with PPV of 0.86. In addition, Garfield et al. (Comparing uterine electromyography activity of antepartum patients versus term labor patients. Am. J. Obstet. Gynecol. 2005; 193: 23-9) documented that the average power density spectrum peak frequency increases with advancing gestation, but increases significantly more during labor.
Prediction of uterine contractile strength is another area gaining attention. Maul et al, (Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery. J. Matem. Fetal Neonatal Med. 2004; 15: 297-301) studied 13 patients with simultaneous IUPC monitoring. They integrated the active intrauterine pressure (above the baseline), and calculated the energy of the electrical bursts by ‘multiplying the sum of the Y-values of the power density spectrum between 0.34 and 1.0 Hz by the duration of the electrical burst in seconds.’ They found a strong correlation (r=0.764, p=0.002) between these and concluded that EHG accurately reflects uterine contractile activity.
Most of the work found in the literature exploits the time course of the EHG in one or at most a few channels. Relatively little investigation into the spatial organization of the uterine electrical activity has occurred. More than 50 years ago, Caldeyro et al. (A Better Understanding of Uterine Contractility through Simultaneous Recording with an Internal and a Seven. Channel External Method. Surgery Gynecology & Obstetrics 1950; 91: 641-50) investigated spatial progression of uterine contractions. They placed both an internal sensor and seven external uterine activity monitors in 18 women in ‘normal, prolonged, and false labors.’ Though statistics are lacking, his group identified several factors that contributed to prolonged labors, the most important of which were absolute intensity of contractions and absence of fundal dominance.
Spatling et al. (External 4-Channel Tocography During Delivery. International Journal of Gynecology & Obstetrics 1994; 46: 291-5) performed four-channel tocography on 54 laboring patients (≥2 cm dilation) for 30-minutes. The four toco signals were plotted in parallel and the time differences in contraction onset between transducers determined by hand. They report that a right fundal onset of the contraction correlated with subsequent vaginal delivery: 2/30 women (7%) with predominant upper right origin of contractions were delivered abdominally, compared with 7/24 (29%) of women with predominance at other sites, p<0.05.
Using IUPC's placed in both the upper and lower uterine segments of laboring women, Margono et al. (Intrauterine Pressure Wave Characteristics of the Upper and Lower Uterine Segments in Parturients with Active-Phase Arrest. Obstetrics and Gynecology 1993; 81: 481-5) studied 15 patients with active phase labor arrest and seven with normal (non-augmented) labor. Mean active pressure was calculated for 12 contractions preceding oxytocin administration, and 12 during the maximal oxytocic effect. Comparisons were made between patients with arrest and those delivering spontaneously and, for the augmented patients, between those that delivered vaginally and those requiring cesarean. In every patient who delivered vaginally (either spontaneously (n=7) or with augmentation (n=9)), the fundal mean active pressure exceeded that of the lower segment. The opposite was true for the abdominally delivered women (n=6): in every patient, the lower segment mean active pressure exceeded that of the fundus both before and after oxytocin augmentation. Interestingly, oxytocin augmentation caused no significant change in the mean active pressure in either segment for either group. The authors note this fundal dominance ‘might be used to gauge the likelihood of success of oxytocin augmentation.’
As noted above, uterine activity is currently monitored by tocodynamometer or IUPC, but neither correlates directly with progress of labor. No current method is effective in predicting labor success, and while serial cervical exams are the gold standard, repeated examinations are limited due to the potential for infection. Early diagnosis of failure to progress in labor will increase patient well-being, decrease hospital costs, and maximize system efficiency. Similarly, there is no reliable method of diagnosing real preterm labor. At present cervical examination is used, and sometimes transvaginal ultrasound or an expensive test of vaginal fluid (fetal fibronectin), but none has an adequate predictive value. A preterm labor detection method would (1) enable preparation for preterm delivery (betamethasone administration to mature lungs, transfer to a tertiary care center) as well as (2) allow those who are not in labor to be sent home sooner.
In summary, the majority of modern research into labor monitoring focuses on detecting intrapartum fetal asphyxia, which affects about 2% of all deliveries, and is the indication for about 10% of cesareans. See Farine D et al., The need for a new outlook on labor monitoring. Journal of Maternal-Fetal & Neonatal Medicine 2006; 19: 161-4. While clearly this research is valuable, a system to better manage labor itself would impact a much larger number of patients. There is a need for a non-invasive means of diagnosing preterm labor, determining labor progress, identifying labor arrest, monitoring response to oxytocin augmentation, accurately distinguishing arrest from very slow labor, and early identification of future labor dystocia. A reliable monitor with these features could improve outcomes of preterm deliveries, reduce the cesarean delivery rate (by identifying those labors that are merely slow), and shorten labor (by aiding in oxytocin titration and early administration, as well as identifying true arrest so cesarean delivery can proceed). The result would be improved patient satisfaction, reduced use of healthcare resources, and reduced infectious complications (by reducing IUPC usage, frequency of cervical exams and labor duration).